Conference high-flyers Gateshead stand in the way of minnows Warrington Town and a place in the FA Cup third round.
Warrington started the weekend in style, pulling off arguably the biggest shock of the first round when they defeated League Two side Exeter City 1-0 on Friday thanks to Craig Robinson's first-half header.
The Northern Premier League Division One North side, who were exactly 100 places below Exeter in the English league pyramid ahead of the match, are the lowest ranked team left in the competition and will have to pull off another shock in order to be in the hat with Premier League big boys such as Chelsea, Manchester United and FA Cup holders Arsenal.
Gateshead currently sit third in the Conference having lost just three times in the league this season and will look to make home advantage count at the Gateshead International Stadium.
Worcester City were also thrust into the spotlight thanks to a 2-1 victory at 1987 winners Coventry City on Sunday.
Their reward is a trip to Glanford Park to face another League One side in the shape of Scunthorpe United.
Blyth Spartans will seek bragging rights when they travel to fellow north east team Hartlepool United, and with the latter currently bottom of League Two a potential upset could well be on the cards.
Non-league sides Chester FC and Dover beat League Two opposition in the shape of Southend United and Morecambe to reach round two, the former were handed a mouth-watering trip to Oakwell to face Barnsley, while the latter also hit the road to play Cheltenham Town.
Other matches see Bury host fellow League Two pacesetters Luton Town, while League One table-toppers Bristol City will welcome Basingstoke Town or AFC Telford to Ashton Gate.
Draw in full:
Oxford United v Tranmere Rovers
Bury v Luton Town
Wrexham v Stevenage/Maidstone United
Scunthorpe United v Worcester City
Colchester United v Peterborough United
Wycombe Wanderers v York City/AFC Wimbledon
Notts County/Accrington Stanley v Yeovil Town
Hartlepool United v Blyth Spartans
Milton Keynes Dons v Chesterfield
Dagenham and Redbridge/Southport v Eastleigh
Gateshead v Warrington Town
Oldham Athletic v Weston-super-Mare/Doncaster Rovers
Havant and Waterlooville/Preston North End v Walsall/Shrewsbury Town
Barnsley v Chester FC
Bradford City v Dartford
Crewe Alexandra/Sheffield United v Plymouth Argyle
Cheltenham Town v Dover Athletic
Cambridge United v Mansfield/Concord Rangers
Bristol City v Basingstoke/AFC Telford
Portsmouth/Aldershot v Northampton Town/Rochdale